Abdulrahman Hunar, Fletcher Paul C, Bullmore Edward, Morcom Alexa M
MRC Cognition & Brain Sciences Unit, University of Cambridge, Cambridge, CB2 7EF, UK.
Brain Mapping Unit, Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Robinson Way, Cambridge CB2 0SZ, UK; Cambridge and Peterborough Foundation trust, Fulbourn Hospital, Cambridge CB21 5EF, UK.
Neuroimage. 2017 Jun;153:211-220. doi: 10.1016/j.neuroimage.2015.03.031. Epub 2015 Mar 21.
The dedifferentiation theory of aging proposes that a reduction in the specificity of neural representations causes declines in complex cognition as people get older, and may reflect a reduction in dopaminergic signaling. The present pharmacological fMRI study investigated episodic memory-related dedifferentiation in young and older adults, and its relation to dopaminergic function, using a randomized placebo-controlled double-blind crossover design with the agonist Bromocriptine (1.25mg) and the antagonist Sulpiride (400mg). We used multi-voxel pattern analysis to measure memory specificity: the degree to which distributed patterns of activity distinguishing two different task contexts during an encoding phase are reinstated during memory retrieval. As predicted, memory specificity was reduced in older adults in prefrontal cortex and in hippocampus, consistent with an impact of neural dedifferentiation on episodic memory representations. There was also a linear age-dependent dopaminergic modulation of memory specificity in hippocampus reflecting a relative boost to memory specificity on Bromocriptine in older adults whose memory was poorer at baseline, and a relative boost on Sulpiride in older better performers, compared to the young. This differed from generalized effects of both agents on task specificity in the encoding phase. The results demonstrate a link between aging, dopaminergic function and dedifferentiation in the hippocampus.
衰老的去分化理论提出，随着人们年龄的增长，神经表征特异性的降低会导致复杂认知能力下降，这可能反映了多巴胺能信号的减少。本药理学功能磁共振成像研究采用随机、安慰剂对照、双盲交叉设计，使用激动剂溴隐亭（1.25mg）和拮抗剂舒必利（400mg），研究了年轻人和老年人中与情景记忆相关的去分化及其与多巴胺能功能的关系。我们使用多体素模式分析来测量记忆特异性：在编码阶段区分两种不同任务情境的分布式活动模式在记忆检索期间恢复的程度。正如预测的那样，老年人前额叶皮质和海马体中的记忆特异性降低，这与神经去分化对情景记忆表征的影响一致。海马体中还存在与年龄相关的记忆特异性多巴胺能线性调节，这反映出与年轻人相比，基线记忆较差的老年人服用溴隐亭后记忆特异性相对增强，而表现较好的老年人服用舒必利后记忆特异性相对增强。这与两种药物在编码阶段对任务特异性的普遍影响不同。结果表明衰老、多巴胺能功能和海马体去分化之间存在联系。
